RESUMO
BACKGROUND AND AIM: Gastric and enteric Helicobacter species have been associated with the pathogenesis of some extragastric diseases. METHODS: We retrospectively investigated the presence of DNA of Helicobacter species in samples of the cancer and the surrounding tumour-free liver tissues of patients with hepatocellular carcinoma (HCC, n=12) and cholangiocarcinoma (CC, n=13). The patients were from an area with low liver cancer incidence and with low hepatitis B and C prevalence. Patients with a benign liver disease (n=24) were included as controls. Paraffin-embedded liver samples were examined by a Helicobacter genus-specific PCR assay as well as group-specific PCR assays for Enterobacteriaceae, Bacteroides, Lactobacillus and Enterococcus. PCR products of positive samples were characterised by denaturing gradient gel electrophoresis (DGGE) and DNA sequencing. RESULTS: PCR assay detected Helicobacter DNA in seven of 12 (58%) and eight of 13 (62%) normal liver tissue specimens from HCC and CC patients, respectively. Two cancer samples from HCC patients were Helicobacter-positive but none of the CC cancers. In the control group, three of 24 (12.5%) patients with a benign liver condition were positive for Helicobacter species (p<0.01 compared to results of tumour-free liver tissue from the cancer patients). DGGE and DNA sequence analysis showed that 90% of the detected PCR products were "H. pylori-like". DNA of some other enteric bacteria was detected in the liver of one cancer patient and one control (4% of all patients). CONCLUSION: The presence of DNA of Helicobacter species in liver specimens, but not of other common gut bacteria, was associated with human hepatic carcinogenesis.
Assuntos
Carcinoma Hepatocelular/microbiologia , Colangiocarcinoma/microbiologia , Helicobacter/isolamento & purificação , Neoplasias Hepáticas/microbiologia , Idoso , DNA Bacteriano/isolamento & purificação , Feminino , Helicobacter/genética , Humanos , Fígado/microbiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos RetrospectivosRESUMO
To investigate if karyotypic features of secondary liver tumors may provide diagnostic information and if the cytogenetic patterns of primary and metastatic colorectal carcinomas (CRC) are different, 33 liver metastases were analyzed: 25 CRC, 4 small intestine carcinoids, 1 ovarian carcinoid, 1 lobular breast cancer, 1 head-and-neck squamous cell carcinoma, and 1 uveal malignant melanoma. Chromosomal aberrations were detected in 24 cases, whereas 5 had normal karyotypes and 4 were uninformative due to lack of mitoses. Trisomy 12 was detected in 2 small intestine carcinoids, suggesting that +12 may be of pathogenetic importance in this tumor type. The breast and head-and-neck carcinomas and the uveal melanoma displayed aberrations previously reported as characteristic in primary tumors, e.g., der(1;16) and deletion of 3p in the breast cancer, losses of 3p and 8p and partial gain of 8q in the head-and-neck carcinoma, and monosomy 3 and i(8)(q10) in the uveal melanoma, indicating that cytogenetic investigations provide important diagnostic information in secondary liver tumors. In the 18 CRC metastases with chromosomal abnormalities, the cytogenetic findings agreed well with previously reported primary CRC. Common numerical abnormalities included gains of chromosomes 7, 11, 13, and 20, and losses of Y, 4, 18, 21, and 22. Structural rearrangements most often affected chromosome bands 1p13, 1q10, 3p21, 5q10, 5q11, 7q10, 8q10, 8q11, 12q13, 16p13, 17p11, 20p13, 20p11, and 20q10, and frequently resulted in losses of 1p, 8p, and 17p, and gains of 5p, 6p, 7p, 8q, and 20q. Comparing the present cases with primary CRC previously analyzed in our department revealed that additional gains of 6p, 6q, 7p, and 20q, and losses of 1p, 4p, 4q, 8p, 18p, 18q, and 22 were more common (P < 0.05) in the metastases, suggesting that these genomic sites harbor genes of importance in the metastatic process of CRC.
Assuntos
Neoplasias do Colo/genética , Neoplasias Hepáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Transtornos Cromossômicos , Neoplasias do Colo/patologia , Feminino , Genoma , Humanos , Cariotipagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-IdadeRESUMO
A 52-year old woman with regular menstruation presented with ascites and abdominal swelling and pain. Bilateral salpingo-oophorectomy, hysterectomy and excision of a few peritoneal nodules was performed. The omentum was firm, giving the impression of carcinoma. The ovaries were enlarged, each containing a non-ruptured cyst with thick yellowish fluid. Microscopy revealed a sclerosing peritonitis in the omentum and nodules. There was a benign cystic teratoma in the left ovary, a corpus luteum in the right ovary. Follow-up has been uneventful for 26 months. The sclerosing peritonitis is considered to be secondary to the ovarian changes, most probably the teratoma.
Assuntos
Neoplasias Ovarianas/complicações , Peritonite/etiologia , Teratoma/complicações , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Peritonite/patologia , Teratoma/patologiaRESUMO
A total of 87 human specimens with 10 histological types of primary neoplasm were studied immunohistochemically with monoclonal antibodies specific for beta-hexosaminidase (Hex). High levels of Hex were found in malignant neoplasms of the skin, cervix, colorectum and in benign as well as neoplastic plasma cells, while no activity was detected in normal epidermis, normal colorectal epithelium or benign naevi. The strongest immunohistochemical reaction was revealed in tumor cells of malignant melanoma. Adenomas and adenocarcinomas of the colorectum showed high levels of Hex with a basal pattern of immunoreactivity more frequent in the tumor cells of adenocarcinomas than adenomas. Fibroblasts and macrophages in the tumors often disclosed immunoreactivity. In most of the sections (including those from plasma cell neoplasms), 7E4 antibody showed low immunoreactivity compared to 2E3, except for non-neoplastic plasma cells, which were as a rule positive with 7E4 and largely negative with 2E3 antibody. This result probably indicated different isoenzymes in benign and neoplastic plasma cells.
Assuntos
Neoplasias/enzimologia , beta-N-Acetil-Hexosaminidases/metabolismo , Adenoma/enzimologia , Medula Óssea/enzimologia , Carcinoma/enzimologia , Neoplasias Colorretais/enzimologia , Histocitoquímica , Humanos , Inflamação/enzimologia , Melanoma/enzimologia , Nevo/enzimologia , Plasmócitos/enzimologia , Plasmocitoma/enzimologia , Neoplasias Cutâneas/enzimologiaRESUMO
Metallothionein is a protein with affinity for metals and is present in several tumors. We examined its immunohistochemical expression in 37 resected primary liver tumors and 117 colorectal metastases. The reaction was intense in the two fibrolamellar hepatocellular carcinomas and in many of the hepatocytes of the pseudotumor case of focal nodular hyperplasia. The reaction was low or moderate in 5 of 17 ordinary hepatocellular carcinomas and in 4 of 14 cholangiocellular carcinomas. There was no reaction in one case each of spindle cell hepatocellular carcinoma, oncocytic adenoma and hemangioendothelial sarcoma. In the metastases, the reaction was low or moderate in 14 cases and negative in 103. Surrounding hepatocytes and stromal cells were more or less positive in all cases.
Assuntos
Carcinoma Hepatocelular/química , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/química , Metalotioneína/análise , Carcinoma Hepatocelular/secundário , Neoplasias Colorretais/patologia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundárioRESUMO
In a model of secondary liver cancer in Wistar rats, the incorporation of tracer doses of pyrimidines and 5-fluoropyrimidines into the acid-soluble fraction, RNA and DNA of several normal tissues and of an experimental adenocarcinoma of the colon transplanted to the liver of rat was determined 90 min after infusion of the substances via the gastroduodenal artery. There was a higher incorporation after injection of FUra than after uracil into tumor RNA. There was very little labeling of DNA by FdUrd but a greater labeling of RNA following injection of this substance than following deoxyuridine in all tissues including tumor except in liver, where it was of the same magnitude. All fluoro compounds gave high labeling of the acid-soluble fraction of the kidney and liver. The experiments will be continued with therapeutic doses of the fluoro compounds.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Hepáticas/metabolismo , Pirimidinas/metabolismo , Animais , Feminino , Neoplasias Hepáticas/secundário , Transplante de Neoplasias , Ratos , Ratos Endogâmicos WFRESUMO
Zymosan--a non-specific macrophage-stimulating agent--reduces tumour take in the liver. The mechanism for this effect is not clear, but it may be mediated via the Kupffer cells and prostaglandins. On the other hand, the Prostaglandin-synthesis inhibitor, indomethacin, inhibits tumour growth. Pretreatment with zymosan (3 mg 100 g-1) for 3 days of two different strains of rats, inoculated in the liver with a hepatoma or an adenocarcinoma cell suspension respectively, reduced tumour take and also initial tumour growth. The effect on tumour take and initial growth was inhibited by concomitant administration of indomethacin (0.2 mg 100 g-1). When zymosan was administered after tumour cell inoculation the growth rate of the hepatoma was retarded, but this effect was not abrogated by indomethacin. Pretreatment with indomethacin had no significant effect on tumour take or initial growth. When given after the tumour was established in the liver, indomethacin reduced the growth rate of the hepatoma, but not of the adenocarcinoma. These results suggest that there are different mechanisms for the effects of zymosan on tumour take and on growth of an established tumour. In immunoincompetent nude mice the effect on the hepatoma was similar to the effect in the rat. In vitro both tumours were insensitive to zymosan and indomethacin. This study confirms that pretreatment with a non-specific macrophage stimulator (zymosan) diminishes tumour take and growth in the liver, that the effect of zymosan on tumour take in the liver is abrogated by indomethacin and that the zymosan effect on tumour take in the liver is at least partly mediated by the Kupffer cells and prostaglandins.
Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Indometacina/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Zimosan/farmacologia , Adenocarcinoma/patologia , Animais , Carcinoma Hepatocelular/patologia , Interações Medicamentosas , Quimioterapia Combinada , Indometacina/administração & dosagem , Fígado/patologia , Neoplasias Hepáticas Experimentais/patologia , Ativação de Macrófagos/efeitos dos fármacos , Camundongos , Transplante de Neoplasias , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Ratos Wistar , Baço/patologia , Zimosan/administração & dosagemRESUMO
In the model of secondary liver cancer in Wistar rats a study was made of the influence of hepatic artery ligation (HAL) on the amount of nucleotides and RNA in tumor and liver tissue and on the uptake of 3H-orotic acid into these compounds and DNA after labelling for 90 minutes. Ten days after inoculation with tumor cells into the central liver lobe, a catheter was placed into the portal vein in all rats and in half of them the hepatic artery was ligated. On days one, three, five or ten, rats were given 3H-orotic acid through the catheter. On day ten 3H-orotic acid was also infused via the femoral vein or intraperitoneally. After HAL there was a decrease in the nucleotide and RNA content of the tumor cells after one, three and five days. There was no such decrease in the liver cells. In all HAL rats there was an increase in the nucleotide and RNA content of the tumor cells at day ten compared to day five. The ratio of RNA to acid soluble fraction labelling in tumors was also increased on day ten in all groups compared to HAL rats at day five. The increased uptake of 3H-orotic acid into tumour RNA at day ten after HAL strongly suggests rearterialization. There was no support for an increased vascularization of the tumor from the portal vein on day three or five. In the liver tissue, HAL had no influence. This experimental study gives no support for the use of hepatic dearterialization followed by intraportal infusion av cytostatic agents in clinical settings.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Ácido Orótico/metabolismo , RNA/biossíntese , Adenocarcinoma/irrigação sanguínea , Animais , DNA/análise , Feminino , Artéria Hepática , Infusões Parenterais , Circulação Hepática , Neoplasias Hepáticas Experimentais/análise , Neoplasias Hepáticas Experimentais/irrigação sanguínea , RNA/análise , Ratos , Ratos Endogâmicos , TrítioRESUMO
This is a prospective pilot investigation of interstitial laser treatment. Twelve patients were treated at 13 sites: seven patients had metastatic or primary liver cancer (with a total of 21 tumour nodules), two had pancreatic carcinoma and four patients had disease at other sites. Treatments were performed with an Nd-YAG laser, using a high power (6 or 10 W), short-time (5 min) technique or a feedback system for temperature regulation at low power (3 W) for 12-16 min. Treatment with high power invariably resulted in rapid carbonization of tissue, which may have contributed to the postoperative death in one patient. The local effect of treatment could be evaluated in 13 hepatic tumours (1.0-10 cm in diameter): 100% necrosis was seen in five and >50% necrosis in the remaining eight. Two tumours were eradicated, five became smaller, and six remained unchanged in size or showed continued growth. Treatment removed or alleviated symptoms in 7/8 symptomatic patients. The feedback system made it possible to avoid carbonization and allowed better control of the tissue temperature. The main problem with either method was to monitor tissue changes in real time, and ultrasonography was found to be of little help in this respect. It is concluded that interstitial laser treatment is a promising method for treatment of tumours. Further development should focus on real-time monitoring and increased volume effect without carbonization.
Assuntos
Terapia a Laser , Neoplasias/radioterapia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Fotocoagulação a Laser , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Projetos Piloto , Estudos Prospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
The cytotoxicity of 5-fluorouracil (5-FU) has been related to its incorporation into RNA and blocking of DNA synthesis. Interferon may enhance the therapeutic efficacy of 5-FU in colorectal cancer. In a model of secondary liver cancer in the rat, the incorporation of 5-FU into the acid-soluble fraction (ASF), RNA and DNA of several normal tissues and the tumor was determined. The liver nucleotide profile and NADPH-cytochrome c reductase activity was examined. A therapeutic dose of 5-FU was given for 2 h via the hepatic artery and the rats were killed 1 h later. Half of them were pretreated with the interferon inducer polyinosinic-polycytidylic acid (poly(I)-poly(C) and interferon. Pretreatment increased the nucleotide (NT)/DNA and RNA/DNA ratios, decreased the cellularity and left the specific RNA labelling unchanged in the bone marrow. In the liver the pretreatment decreased the NT/DNA and RNA/DNA ratios, (F)UTP, and the NADPH-cytochrome c reductase activity. The 5-FU incorporation into liver DNA decreased. No changes were found in the tumor. The pretreated rats decreased in body weight. A decreased RNA synthesis in the liver might indicate a decreased 5-FU metabolism, explaining the increased 5-FU AUC in the clinic at interferon treatment.
Assuntos
Adenocarcinoma/secundário , Neoplasias do Colo/metabolismo , Fluoruracila/metabolismo , Interferon Tipo I/farmacologia , Neoplasias Hepáticas/secundário , Fígado/metabolismo , Poli I-C/farmacologia , RNA Neoplásico/biossíntese , RNA/biossíntese , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/metabolismo , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Neoplasias do Colo/induzido quimicamente , DNA/metabolismo , Dimetilidrazinas , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Masculino , RNA/efeitos dos fármacos , RNA Neoplásico/efeitos dos fármacos , Ratos , Ratos Wistar , Ribonucleotídeos/metabolismoRESUMO
Two experiments were performed with a chemically induced hepatoma in the rat. In the first, tumors were inoculated subcutaneously into both flanks. After 10 days, when all rats had tumors, treatment was given intravenously on two successive days with 10 mg carmustine/kg body weight/day. All control rats displayed growing tumors and had to be killed 12 days after treatment. Treated rats initially lost weight with a slight increase in tumor size. After 3 weeks all tumors disappeared and the rats grew normally. After 4 months the rats were killed and had no tumors. In a second experiment, tumors were inoculated under the liver capsule. Treatment was given via the hepatic artery. Control rats had large tumors after 2 weeks and had to be killed. All treated rats were without tumors at sacrifice. One of them developed a liver cyst and was killed after 3 months, the others after 4 months.
Assuntos
Carmustina/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Animais , Neoplasias Hepáticas Experimentais/induzido quimicamente , Transplante de Neoplasias , Ratos , Ratos WistarRESUMO
UNLABELLED: Rats were inoculated via the portal vein with a suspension of tumor cells from a transplantable dimethylhydrazine-induced adenocarcinoma of rat colon. In one set of experiments, the bioreductive drug RSU-1069 was injected once via the portal vein with or without degradable starch microspheres (DSM) 10 mins after tumour cell inoculation. In another set the immunostimulator liposomal-encapsulated muramyl tripeptide phosphatidyl-ethanolamine (MTP-PE) was injected via the portal vein or penile vein 1 day before tumour-cell inoculation and then twice a week. The experiments were finished after 2 to 3 weeks. Tumour take, numbers and volumes were measured. RESULTS: RSU-1069 enhanced tumour growth when combined with DSM. Liposomal MTP-PE also increased tumour growth. CONCLUSION: A bioreductive drug combined with microspheres, known to suppress the growth of an established tumour, may enhance its growth in the adjuvant setting. An accepted immunostimulator may enhance tumour take. Drugs used for the treatment of tumours must be carefully employed, if applied in an adjuvant setting. The effect on the normal immune system should be further studied.
Assuntos
Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adjuvantes Imunológicos/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias Hepáticas Experimentais/secundário , Misonidazol/análogos & derivados , Fosfatidiletanolaminas/efeitos adversos , Acetilmuramil-Alanil-Isoglutamina/administração & dosagem , Acetilmuramil-Alanil-Isoglutamina/efeitos adversos , Animais , Portadores de Fármacos , Lipossomos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Masculino , Microesferas , Misonidazol/administração & dosagem , Misonidazol/efeitos adversos , Fosfatidiletanolaminas/administração & dosagem , Ratos , Ratos WistarRESUMO
Rats were inoculated subcutaneously into both flanks with a transplantable adenocarcinoma of the colon. They were treated intravenously with either 5-FUrd (5-fluorouridine) or 5-FdUrd (5-fluoro-2'-deoxyuridine) with or without addition of dipyridamole 20 and 30 min later, respectively, for 3 consecutive days. Dipyridamole improved the antitumor activity of 5-FUrd but decreased that of 5-FdUrd.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dipiridamol/administração & dosagem , Floxuridina/administração & dosagem , Uridina/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Dipiridamol/farmacologia , Sinergismo Farmacológico , Floxuridina/metabolismo , Masculino , Transplante de Neoplasias , Ratos , Ratos Endogâmicos , Uridina/administração & dosagem , Uridina/metabolismoRESUMO
Rats with an adenocarcinoma of the colon implanted into the liver were treated by a bolus injection of adriamycin by the hepatic artery. In addition, vascular occlusions were performed in the following three ways. 1. The hepatic artery was ligated (HAL) immediately after adriamycin injection. 2. The portal venous branch nourishing the tumor was ligated immediately after adriamycin injection. 3. The Pringle maneuvre (clamping of the hepatic artery, the portal vein and the common bile duct) was performed during 5 min before and 10 min after injection. Tumor size was measured at operation and 6 and 12 days later in the first experiment, 7 days later in the other two experiments. The combination of adriamycin and HAL retarded tumor growth at day 6 as compared to controls, adriamycin alone and HAL alone. The differences were not significant at day 12. The other vascular occlusions did not improve the antitumor effect of adriamycin.
Assuntos
Adenocarcinoma/terapia , Ducto Colédoco/cirurgia , Doxorrubicina/uso terapêutico , Artéria Hepática/cirurgia , Neoplasias Hepáticas/terapia , Veia Porta/cirurgia , Adenocarcinoma/tratamento farmacológico , Animais , Peso Corporal , Doxorrubicina/administração & dosagem , Injeções Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Ratos , Ratos EndogâmicosRESUMO
The effect of the cytostatic nitrosourea drugs TCNU and BCNU on tumor growth was studied in rats with a transplantable colon adenocarcinoma implanted into the liver. The drugs were given as a single dose into the hepatic artery alone or together with degradable starch microspheres (DSM). The effect of the treatment on tumor growth was measured 7 days later. Compared to control animals, TCNU decreased tumor growth. BCNU alone did not significantly decrease tumor growth. The antitumor effect of both drugs was significantly improved by DSM. The addition of DSM to the drugs caused liver damage in a few rats. There were no differences between different treatment groups regarding body weight changes. DSM may protect bone marrow against BCNU toxicity. Injection of DSM alone had no effect either on tumor growth or on survival.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Carmustina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Nitrosoureia/administração & dosagem , Taurina/análogos & derivados , Animais , Carmustina/uso terapêutico , Portadores de Fármacos , Artéria Hepática , Injeções Intra-Arteriais , Masculino , Microesferas , Compostos de Nitrosoureia/uso terapêutico , Ratos , Ratos Endogâmicos , Amido , Taurina/administração & dosagem , Taurina/uso terapêuticoRESUMO
The effect of intravenously injected tauromustine (TCNU) on tumor growth and body weight was studied in rats with subcutaneously implanted experimental carcinomas. With a colonic tumor, a single dose or that dose split on 4 consecutive days gave the same tumor growth delay but the body weight loss was less at the split dose. Injection of the single dose for 1 min, 30 min or 2 h each had the same effect. Rats of another strain were implanted with a hepatoma. 9 out of 10 rats were cured. A late effect was body weight loss due to disturbed growth of the teeth.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Compostos de Nitrosoureia/administração & dosagem , Taurina/análogos & derivados , Animais , Benzidinas , Neoplasias do Colo/induzido quimicamente , Dimetilidrazinas , Ensaios de Seleção de Medicamentos Antitumorais , Injeções Intravenosas , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Ratos , Ratos Endogâmicos , Organismos Livres de Patógenos Específicos , Taurina/administração & dosagemRESUMO
The degradable starch microspheres (DSM) used have a size of 45 microns and are dissolved by amylase in blood. After intraarterial administration of a mixture of DSM and cytostatic drugs the coinjected drugs remain for a longer time in the target tissue/tumor. A transient hypoxia occurs. Systemic exposure of drugs is decreased. Rats with a carcinoma implanted into the liver were given DSM and drugs via the hepatic artery. DSM did not significantly increase the incorporation of 5-fluorouracil (5-FU) into liver tumor RNA. The incorporation of 5-FU into intestinal and bone marrow RNA increased. DSM increased the antitumor effect of doxorubicin, tauromustine, carmustine and RSU-1069 (aziridine 2-nitroimidazole). Side effects, such as liver and gastric necroses and body weight loss, appeared in some rats. The toxic overspill to the stomach seemed to be reduced by giving the DSM in two parts, with all the cytotoxic drug in the first part. The effect on liver and tumor was not decreased by this procedure. DSM alone had no anti-tumor effect. DSM alone decreased liver UDP-glucuronic acid in tumor-free rats, given either by the hepatic artery or, in the double dose, by the portal vein. DSM alone did not increase liver NADPH-cytochrome c reductase activity or serum ASAT (aspartate-aminotransferase) or ALAT (alanine-aminotransferase), indicating that the DSM are inert to the liver, when infused into the tributary vessels.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Animais , Carmustina/administração & dosagem , Doxorrubicina/administração & dosagem , Fluoruracila/administração & dosagem , Infusões Intra-Arteriais , Fígado/enzimologia , Fígado/patologia , Neoplasias Hepáticas/irrigação sanguínea , Microesferas , Misonidazol/administração & dosagem , Misonidazol/análogos & derivados , Necrose , Compostos de Nitrosoureia/administração & dosagem , Ratos , Ratos Wistar , Organismos Livres de Patógenos Específicos , Amido/administração & dosagem , Estômago/irrigação sanguínea , Taurina/administração & dosagem , Taurina/análogos & derivadosRESUMO
The cytotoxicity of 5-FU and 5-FUrd, given via the hepatic artery, was measured by its incorpotation into the acid soluble fraction, RNA and DNA in normal tissues and an adenocarcinoma transplanted into the liver in rats. Drugs inhibiting the membrane transport of, especially, nucleosides were simultaneously administered by a femoral vein to modulate the cytotoxicity. None of them (dipyridamole, lidoflazine nor dilazep) had any statistically significant influence on the tumour. Dipyridamole and lidoflazine decreased the incorporation of 5-FU into the acid soluble fraction, RNA and DNA of the intestine. Dipyridamole probably decreased the incorporation of 5-FUrd into the acid soluble fraction and RNA of the intestine. Lidoflazine has not been tested with 5-FUrd. Dipyridamole increased the incorporation of 5-FU into the acid soluble fraction of liver, bone marrow and kidney, and of 5-FUrd into the acid soluble fraction of liver and bone marrow and liver RNA. Lidoflazine had fewer adverse effects. Both dipyridamole and lidoflazine increased the combined peak of UTP and FUTP in the liver, and dipyridamole also in the intestine of 5-FU treated rats. Dipyridamole which undergoes an enterohepatic circulation increased the combined peak of UDP-glucuronic acid and FUDP-glucuronic acid in 5-FU and 5-FUrd treated rats, as well as UDP-glucuronic acid in rats given neither 5-FU nor 5-FUrd in the liver. Membrane transport inhibitors seem to offer the opportunity to protect normal tissues from the cytotoxicity of 5-fluoropyrimidines, but the tissues can also be more exposed.
Assuntos
Adenocarcinoma/metabolismo , Fluoruracila/toxicidade , Neoplasias Hepáticas/metabolismo , Uridina/análogos & derivados , Adenocarcinoma/tratamento farmacológico , Animais , Transporte Biológico/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Membrana Celular/metabolismo , DNA de Neoplasias/metabolismo , Dipiridamol/farmacologia , Metabolismo Energético/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Lidoflazina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Masculino , RNA Neoplásico/metabolismo , Ratos , Ratos Endogâmicos , Uridina/toxicidadeRESUMO
Cytostatic treatment of liver metastases from colorectal cancer has been of limited value. Higher drug levels in the target substances of the tumor may improve the results. It was the aim of this investigation to examine the effect of PALA (N-phosphonacetyl-L-aspartate) and D-glucosamine on the level of uracil nucleotides in the liver and in an N-methyl-N-nitrosoguanidine-induced adenocarcinoma of the colon transplanted to the liver of rats, and on the incorporation of 3H-FUrd into the acid-soluble fraction, the RNA and the DNA of the tumor and of several normal tissues. Combined treatment with PALA and D-glucosamine reduced the UTP pool in the liver and the tumor. D-glucosamine alone increased UDP-N-acetyl-hexosamine in liver tissue. Pretreatment with PALA and D-glucosamine increased incorporation of 3H-FUrd into RNA of the liver and kidney, and into the DNA fraction of the liver, but had no effect on 3H-FUrd incorporation in the tumor.
Assuntos
Adenocarcinoma/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Ácido Aspártico/análogos & derivados , Glucosamina/farmacologia , Neoplasias Hepáticas/secundário , Fígado/metabolismo , Compostos Organofosforados/farmacologia , Ácido Fosfonoacéticos/farmacologia , RNA Ribossômico/antagonistas & inibidores , Uridina/análogos & derivados , Animais , Ácido Aspártico/farmacologia , DNA de Neoplasias/metabolismo , Feminino , Neoplasias Intestinais/patologia , Neoplasias Hepáticas/metabolismo , Transplante de Neoplasias , Ácido Fosfonoacéticos/análogos & derivados , RNA Neoplásico/metabolismo , Ratos , Ratos Endogâmicos , Uridina/metabolismoRESUMO
BACKGROUND: In this study, electrochemotherapy (ECT), i.e. tumour treatment based on local augmentation of intracellular drug delivery from short, intense electric pulses, was evaluated in rats with an adenocarcinoma implanted into the liver. Tumour response and concentrations of macrophages and T-lymphocytes (CD4 and CD8) in and around the tumour were measured. MATERIALS AND METHODS: Rats were treated with permeabilizing electric pulses, bleomycin, or both, eight days after implantation of the tumour, while one group received sham treatment. RESULTS: Treatment with electric pulses and bleomycin resulted in a significantly reduced lesion volume and 92% cure rate (12 out of 13, p<0.0002 compared to the other treatment groups). The highest concentration of CD8 lymphocytes was found in tumours treated with electric pulses and bleomycin. Macrophages were found mainly in tumours treated with electric pulses, with or without bleomycin. CONCLUSION: Electrochemotherapy using millisecond exponential pulses and bleomycin is efficient in a rat liver tumour model and appears to stimulate the host's immune system.